Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases
Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases
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DOI：
10.1016/j.bmc.2009.01.064
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发表时间：
2009-03-01
影响因子：
3.5
通讯作者：
Mizushina, Yoshiyuki
中科院分区：
文献类型：
--
作者：
Kimura, Takuma;Takeuchi, Toshifumi;Mizushina, Yoshiyuki
青霉醇A（1）和B（2）是从真菌Penicillium daleae K. M. Zalessky），并通过光谱分析确定了它们的结构。这些化合物选择性地抑制真核Y家族DNA聚合酶（pols）的活性（即，POLS η、I和κ），并且化合物1是比化合物2更强的抑制剂。在哺乳动物Y家族pol中，化合物1和2最强烈地抑制小鼠pol活性，IC 50值分别为19.8和32.5 μ M。另一方面，许多其他pols的活动，如A-家庭（即，聚γ），B族（即，pols α，δ和ε）或X族（即，pol β、λ和末端脱氧核苷酸转移酶）和一些DNA代谢酶，如pol α的小牛引发酶、人免疫缺陷病毒1型（HIV-1）逆转录酶、人端粒酶、T7 RNA聚合酶、小鼠IMP脱氢酶（II型）、人拓扑异构酶I和II、T4多核苷酸激酶或牛脱氧核糖核酸酶I，不受这些化合物的影响。总之，这是第一份关于哺乳动物Y家族pols有效抑制剂的报告。(C)2009爱思唯尔有限公司保留所有权利。
Penicilliols A (1) and B (2) are novel 5-methoxy-3(2H)-furanones isolated from cultures of a fungus (Penicillium daleae K.M. Zalessky) derived from a sea moss, and their structures were determined by spectroscopic analyses. These compounds selectively inhibited activities of eukaryotic Y-family DNA polymerases (pols) (i.e., pols eta, iota and kappa), and compound 1 was a stronger inhibitor than compound 2. Among mammalian Y-family pols, mouse pol iota activity was most strongly inhibited by compounds 1 and 2, with IC50 values of 19.8 and 32.5 mu M, respectively. On the other hand, activities of many other pols, such as A-family (i.e., pol gamma), B-family (i.e., pols alpha, delta and epsilon) or X-family (i.e., pols beta, lambda and terminal deoxynucleotidyl transferase), and some DNA metabolic enzymes, such as calf primase of pol alpha, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse IMP dehydrogenase (type II), human topoisomerases I and II, T4 polynucleotide kinase or bovine deoxyribonuclease I, are not influenced by these compounds. In conclusion, this is the first report on potent inhibitors of mammalian Y-family pols. (C) 2009 Elsevier Ltd. All rights reserved.